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胸腺癌中程序性死亡配体 1 和程序性死亡受体 1 表达的预后价值。

Prognostic Value of Programmed Death Ligand 1 and Programmed Death 1 Expression in Thymic Carcinoma.

机构信息

Department of Surgery, Kurume University School of Medicine, Kurume, Japan.

Department of Pathology, Kurume University School of Medicine, Kurume, Japan.

出版信息

Clin Cancer Res. 2016 Sep 15;22(18):4727-34. doi: 10.1158/1078-0432.CCR-16-0434. Epub 2016 May 10.

Abstract

PURPOSE

The immune checkpoint of the programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway is believed to play an important role in evasion of host antitumor immune surveillance in various malignancies; however, little is known about its role in thymic carcinoma. This study investigated PD-1/PD-L1 expression and its association with clinicopathologic features, the expression of immune-related proteins in tumor-infiltrating lymphocytes (TIL), and patient prognosis.

EXPERIMENTAL DESIGN

PD-L1 and PD-1 expression was evaluated by IHC in 25 thymic carcinoma tissue specimens. Copy number alterations of the PD-L1 gene in 11 cases were assessed in formalin-fixed, paraffin-embedded material using qRT-PCR.

RESULTS

Compared with normal subjects, 3 thymic carcinoma patients showed an increase in PD-L1 copy number, whereas 8 did not. PD-L1 was significantly overexpressed in cases with copy number gain as compared with normal cases. High PD-L1 expression was associated with higher disease-free and overall survival rates as compared to cases with low expression. Prognostic analysis revealed low PD-L1 expression and high number of PD-1(+) TILs as significant predictors of poor survival, together with Masaoka-Koga stage IVa/IVb disease and incomplete resection. In the quantitative analysis of TILs, PD-L1 expression correlated proportionally with the number of infiltrating CTLs.

CONCLUSIONS

Here, for the first time, we report that PD-L1 and PD-1 expression might be useful prognostic predictors in thymic carcinoma. Further studies are expected to substantiate the prognostic value of PD-L1 and PD-1 expression, and the potential efficacy of targeting the PD-1/PD-L1 pathway in thymic carcinoma via immunotherapy. Clin Cancer Res; 22(18); 4727-34. ©2016 AACR.

摘要

目的

程序性死亡受体 1/程序性死亡配体 1(PD-1/PD-L1)通路的免疫检查点被认为在多种恶性肿瘤中逃避宿主抗肿瘤免疫监视中发挥重要作用;然而,其在胸腺癌中的作用知之甚少。本研究调查了 PD-1/PD-L1 的表达及其与临床病理特征的关系、肿瘤浸润淋巴细胞(TIL)中免疫相关蛋白的表达以及患者预后。

实验设计

通过免疫组化(IHC)评估 25 例胸腺癌组织标本中 PD-L1 和 PD-1 的表达。使用 qRT-PCR 在福尔马林固定、石蜡包埋材料中评估 11 例 PD-L1 基因的拷贝数改变。

结果

与正常对照相比,3 例胸腺癌患者 PD-L1 拷贝数增加,而 8 例患者 PD-L1 拷贝数无变化。与正常病例相比,拷贝数增加的病例 PD-L1 表达明显上调。与低表达病例相比,高 PD-L1 表达与更高的无病生存率和总生存率相关。预后分析显示,低 PD-L1 表达和高 PD-1(+)TIL 数量是生存不良的显著预测因子,与 Masaoka-Koga 分期 IVa/IVb 疾病和不完全切除相关。在 TIL 的定量分析中,PD-L1 表达与浸润 CTL 的数量成比例相关。

结论

在这里,我们首次报道 PD-L1 和 PD-1 的表达可能是胸腺癌有用的预后预测因子。预计进一步的研究将证实 PD-L1 和 PD-1 表达的预后价值,以及通过免疫疗法靶向 PD-1/PD-L1 通路在胸腺癌中的潜在疗效。临床癌症研究;22(18);4727-34。©2016AACR。

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